Structures and Thermodynamics of Alzheimer’s Amyloid-β Aβ(16−35) Monomer and Dimer by Replica Exchange Molecular Dynamics Simulations: Implication for Full-Length Aβ Fibrillation
Bibliographic record
Abstract
Many proteins display a strand-loop-strand motif in their amyloid fibrillar states. For instance, the amyloid beta-protein, Abeta1-40, associated with Alzheimer's disease, displays a loop at positions 22-28 in its amyloid fibril state. It has been suggested that this loop could appear early in the aggregation process, but quantitative information regarding its presence in small oligomers remains scant. Because residues 1-15 are disordered in Abeta1-42 fibrils and Abeta10-35 forms fibrils in vitro, we select the peptide Abeta16-35, centered on residues 22-28 and determine the structures and thermodynamics of the monomer and dimer using coarse-grained implicit solvent replica exchange molecular dynamics simulations. Our simulations totalling 5 mus for the monomer and 12 micros for the dimer show no sign of strong secondary structure signals in both instances and the significant impact of dimerization on the global structure of Abeta16-35. They reveal however that the loop 22-28 acts as a quasi-independent unit in both species. The loop structure ensemble we report in Abeta16-35 monomer and dimer has high similarity to the loop formed by the Abeta21-30 peptide in solution and, to a lesser extent, to the loop found in Abeta1-40 fibrils. We discuss the implications of our findings on the assembly of full-length Abeta.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".